Abstract
INTRODUCTION
Disturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer’s disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes.
METHODS
We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo magnetic resonance imaging, to investigate early capillary dysfunction in C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax (Tg-SwDI) mice without memory impairment. We also assessed the efficacy of carbonic anhydrase inhibitors (CAIs) in preventing capillary flow disturbances.
RESULTS
Our study revealed capillary flow disturbances associated with alterations in capillary morphology, adhesion molecule expression, and amyloid beta (Aβ) load in 9- to 10-month-old Tg-SwDI mice without memory impairment. CAI treatment ameliorated these capillary flow disturbances, enhanced oxygen availability, and reduced Aβ load.
DISCUSSION
These findings underscore the importance of capillary flow disturbances as early biomarkers in presymptomatic AD and highlight the potential of CAIs for preserving vascular integrity in the early stages of AD.
Highlights
Uncovered early capillary dysfunction in a presymptomatic Alzheimer’s disease (AD) mouse model.
Evidence linking capillary stalls and capillary dysfunction with oxygen delivery issues in AD.
Novel use of carbonic anhydrase inhibitors to prevent early capillary flow disturbances in AD.
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This post is Copyright: Eugenio Gutiérrez‐Jiménez,
Peter Mondrup Rasmussen,
Irene Klærke Mikkelsen,
Sreekanth Kura,
Signe K. Fruekilde,
Brian Hansen,
Luca Bordoni,
Jasper Carlsen,
Johan Palmfeldt,
David A. Boas,
Sava Sakadžić,
Sergei Vinogradov,
Mirna El Khatib,
Jaime Ramos‐Cejudo,
Boris Wied,
Desiree Leduc‐Galindo,
Elisa Canepa,
Adam C. Mar,
Begona Gamallo‐Lana,
Silvia Fossati,
Leif Østergaard | March 26, 2025